The human interleukin-2 receptor is being studied to understand critical components of the T cell immune response in normal and neoplastic cells. When T-cells are activated by antigen or mitogenic lectin, both IL-2 and IL-2 receptor expression are induced. IL-2 and IL-2 receptors regulate the magnitude and duration of the T-cell immune response, based on the amount of O:-2 produced, the levels of receptors expressed, and the time course of each of these events. Whereas a low level of intermediate affinity IL-2 receptors are expressed on resting cells, following antigen stimulation, both high and low affinity IL-2 receptor expression is potently induced. Three chains of the IL-2 receptor are now known to exist, namely IL-2Ralpha, Il02Rbeta, and gammac, with IL-2Ralpha and IL- 2Rbeta being significantly regulated at the level of transcription. This lab was the first to analyze the promoters of each of these genes. In the past year, the group has made major advances: (1) A new enhancer in the IL-2Ralpha 5' regulatory region has been delineated and functional coordination between this enhancer and the previously identified upstream enhancer is indicated. (2) The critical cis-acting elements in the IL- 2Rbeta promoter were delineated and three regions with enhancer activity have been characterized. (3) Major progress has been made in identifying transcription factors responsible for the regulation of expression of both the IL-2Ralpha and IL-2Rbeta chain genes. A new PMA inducible factor has been characterized and rapidly induced latent transcription factors (known as STAT proteins for signal transducers and activators of transcription) have been found to be induced by a number of cytokines. These findings therefore are critical not only to an understanding of IL- 2 receptor gene regulation but also extend to the regulation of other T- cell activation genes.